Antidotal effects of methylene blue against cyanide neurological toxicity: in vivo and in vitro studies,Annals of the New York Academy of Sciences

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Antidotal effects of methylene blue against cyanide neurological toxicity: in vivo and in vitro studies
Annals of the New York Academy of Sciences ( IF 4.1 ) Pub Date : 2020-05-06 , DOI: 10.1111/nyas.14353
Philippe Haouzi ₁ , Marissa McCann ₁ , JuFang Wang ₂ , Xue-Qian Zhang ₂ , Jianliang Song ₂ , Ilker Sariyer ₃ , Diane Langford ₃ , Maryline Santerre ₄ , Nicole Tubbs ₁ , Annick Haouzi-Judenherc ₅ , Joseph Y Cheung _{2,

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Affiliation

The aim of the present study was to determine whether methylene blue (MB) could directly oppose the neurological toxicity of a lethal cyanide (CN) intoxication. KCN, infused at the rate of 0.375 mg/kg/min intravenously, produced 100% lethality within 15 min in unanaesthetized rats (n = 12). MB at 10 (n = 5) or 20 mg/kg (n = 5), administered 3 min into CN infusion, allowed all animals to survive with no sequelae. No apnea and gasping were observed at 20 mg/kg MB (P < 0.001). The onset of coma was also significantly delayed and recovery from coma was shortened in a dose‐dependent manner (median of 359 and 737 seconds, respectively, at 20 and 10 mg/kg). At 4 mg/kg MB (n = 5), all animals presented faster onset of coma and apnea and a longer period of recovery than at the highest doses (median 1344 seconds, P < 0.001). MB reversed NaCN‐induced resting membrane potential depolarization and action potential depression in primary cultures of human fetal neurons intoxicated with CN. MB restored calcium homeostasis in the CN‐intoxicated human SH‐SY5Y neuroblastoma cell line. We conclude that MB mitigates the neuronal toxicity of CN in a dose‐dependent manner, preventing the lethal depression of respiratory medullary neurons and fatal outcome.

中文翻译：

亚甲蓝对氰化物神经毒性的解毒作用：体内和体外研究

本研究的目的是确定亚甲蓝 (MB) 是否可以直接对抗致命氰化物 (CN) 中毒的神经毒性。KCN 以 0.375 mg/kg/min 的速度静脉内输注，在 15 分钟内对未麻醉的大鼠（n = 12）产生 100% 的致死率。10 (n = 5) 或 20 mg/kg (n = 5) 的 MB，在 CN 输注 3 分钟后给药，使所有动物都能存活而没有后遗症。在 20 mg/kg MB 下未观察到呼吸暂停和喘气（P < 0.001）。昏迷的发作也显着延迟，昏迷的恢复以剂量依赖性方式缩短（中位数分别为 359 和 737 秒，在 20 和 10 mg/kg 时）。在 4 mg/kg MB (n = 5) 时，与最高剂量相比，所有动物都表现出更快的昏迷和呼吸暂停发作以及更长的恢复期（中位数 1344 秒，P < 0.001）。MB 在 CN 中毒的人类胎儿神经元的原代培养物中逆转了 NaCN 诱导的静息膜电位去极化和动作电位抑制。MB 在 CN 中毒的人 SH-SY5Y 神经母细胞瘤细胞系中恢复了钙稳态。我们得出结论，MB 以剂量依赖性方式减轻 CN 的神经元毒性，防止呼吸延髓神经元的致命抑制和致命结果。

更新日期：2020-05-06

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